Manufacture of sodium salt of 3.3&#39;-diamino-4.4&#39;-dihydroxyarsenobenzene



- purities; Products which have heretofore Patented l )ec. 2 l,. 1 9 26.v "UNITED 'ST Ares. IENT- OFF ICE.

PHILIP A. KOBER, on HAs'rmes-oN-nunson, new YORK.

nanuracronn on sonIuM SALT on 3.3-DIAMINO-4.4':DIHYDROXYARSENOBENZENE.

No Drawing.

This invention relates to the production of a stable sodium saltof3--diamino-4%4'-' dihydroxy arseno-benzene.

In order to inject arsphenamine into the body, it is desirable toconvert it, after dissolving, from the hydrochloride, which is an acidsalt, into an alkaline salt. Thus, when a solution of thedihydrochloride is treatedwith causticv soda solution it is convertedinto the disodium, salt of-the free base. 'This neutralizationis'commonly efiected by the physician at the time of administration.

It has not heretofore been feasible, in' so far 'as I am aware,toprepare and isolate the pure sodium salt in a stable form, so that itis directly available for use. Thus U. S. Patent No. 1,191,997 pointsoutthat the pure alkali metal salts of arsphenamine base are unstable, andthis patent proposes been available, as made by those skilled in theart, thus. contain around 43 to 49 per cent of impurities; and the U. S.Hygenic Laboratory finds and allows the arsenic content of the sodiumsalt of arsphenamine base of different manufacturers to be from around19 to 21 per cent, although thechemically pure anhydrous arsphenaminecalls for an arsenic content of about 36.6 per cent.

I have now found that a substantially pure sodium salt of arsphenaminebase can be prepared in a simple and advantageous pended in 400 cc. of

manner and in a stable form, with an arsenic content approximating thetheoretical, and free from objectionable impurities such as alcohol ofcrystallization, or as addition products. The invention will be furtherillustrated by the following more detailed description of the preferredpractice there- 36.6 grams of arsphenamine base are suedistilled waterand dis: solved in 50 cc. of hydroxide. 1000 cc. of boiling water arethen added, and then enough five normal hytwice normal sodiumApplication filed April 12, 1920. Serial No. 373.285.

drochloric to reprecipitate all of the arsphen amine base, about 20 cc.of the five normal hydrochloric acid being suificient. The precipitateis then filtered and washed with distilled water. This preliminarytreatmeant is for the purpose of unifying the arsphenamine baseand'separ ting it from impurities with which it may be admixed. Theprecipitated and. filtered product is, therefore, a product ofhighpurity.

The recipitated base, after filtering and washing, and while st-illadmixed with the Water remaining after the filtration, is

agitated or whipped'or beaten into a stiff paste or cream. There is thenadded, with stirring, about 83 cc. of twice normal caustic soda untilalmost all of the paste has been dissolved' I Excess caustic soda isavoided,-

and this can readily be effected by leaving a small amount ofthe.precipitate undissolved, thereby avoiding any excess of free alkali.The solution of the sodium salt thus obtained is filtered through cottonto remove undissolvedmaterial and then evaporated to dryness under ahigh vacuum, for example, a vacuum of two to ten millimetres ofpressure, that is, an absolute pressure corresponding to such a.mercury' column,

and at a relatively low temperature that is at a suitable water bathtemperature of about 50 to C. The dried product may contain one or moremolecularproportions of water, if it is not completely dried. In theabove example, if a more concentrated caustic soda solutionis used, acorrespondingly less amount of water will require tog be evaporated.

The sodium salt produced in the manner above described is a productofhigh purity and is likewise a product of great stability, well adaptedfor manufacture and storage, for example, in sealed ampules containingan indifferent gas. It is f ee from'excess free alkali, and also freerom any objec tionable by-products/ I claim:

, 1. In a method of producing the sodium salt of'arsphenamine basewherein the arsphenaniine base is purified in an aqueous solution, thesteps of dissolvingthe purified base while still admixed with water in acaustic soda solution while avoiding excess of caustic soda, andevaporating the resulting. solution to dryness under a high vacuum. 2.Themethod 0f produclng the sodium salt of arsphenamine base which:comprises dissolving purified arsphenamine base in caustic sodasolution, using insufficient caustic soda to dissolve all of the base,thereby avoiding excess of free alkali, filtering the resultin solutionand evaporating the solution to dryness under a vacuum sufficient tocause evaporation at a relatively low temperature;

3. In a method of producing the sodium salt of arsphenami-ne basewherein a purified base is obtained by dissolving arsphenau'iine baseincaustic sodasolution and forming a hot solution, reprecipitating thebase from suchsolution with hydrochloric acid, and filtering and Washingthe precipitate, the steps of dissolving the precipitate while stilladmixed with water in caustic soda while avoiding excess of free alkali,and evaporating the resulting solution to dryness under a Vacuumsufiicient to cause evaporation at a relatively vlow temperature.

4, The method of producing the sodium salt of arsphenamine base whichcomprises dissolving apurified arsphenamine base in flocculent formadmixed with water in canstic soda solution, avoiding excess of causticsoda, and evaporating the resulting solution to dryness under avacuumsufficient to cause evaporation at a relatively low temperature.

5. As a new product, the sodium salt of arsplienamine base in'the formof the sodium salt of the free base, the product being stable,substantially pure. and containing approximately 3G.6% of arsenic.

In testimony whereof I afiix my signature,

P'HiLIP A. KOBER.

